The model system of rat cortical neurons, which are grown in dissociated cell culture, and have a long survival time, with regular formation of excitatory and inhibitory synapses, will be the focus of a series of interdisciplinary studies of transmitter function and regulation. Special attention will be given to GABA neurons and GABA synapses. Extensive evidence supports the notion that GABA is the main inhibitory transmitter in this system, possibly the only one. About 30% of the neurons found at 3-5 weeks of age appear to be GABA neurons, based upon GABA uptake autoradiography: 1. We shall attempt to separately study the regulation of pre- and postsynaptic components of GABA synapses. In vivo evidence from other types of synapses, principally monoamine synapses, supports the concept that the post-synaptic receptors are largely "hard-wired" while the pre-synaptic elements may be subject to extensive environmental influences. Does the presence of glial cells alter the number of GABA neurons or the amount of GABA made per GABA neuron? If GABA synthesis is suppressed over a period of days or weeks, will the number and properties of GABA receptors change? 2. What is the effect of chronic treatment with transmitter-active drugs (such as inhibitors of GABA-transaminase) on synaptic function? Can we selectively modify GABA synapses so as to increase or decrease synaptic "efficacy"? 3. What effects do anticonvulsants, neuroleptics, and benzodiazepines have upon synaptogenesis and neuronal development in cortical cultures? 4. Is synapse formation associated with detectable changes in cell surface properties, receptor density and topography, and cellular metabolic events? These studies will make use of modern neural probes such as lectins, cholera toxin, and deoxyglucose.